We propose to continue and extend our studies on molecular[unreadable] events leading to poliovirus replication and our analysis of[unreadable] neutralization antigenic sites of the virus particle. Specifically,[unreadable] we propose to analyze the structure and function(s) of the 5' non-[unreadable] coding region of poliovirus RNA, to determine processes of protein[unreadable] modification and of proteolytic cleavage of the poliovirus[unreadable] polyprotein, to investigate the structure and substrate recognition[unreadable] of the two virus-encoded proteinases, and to analyze components[unreadable] of viral RNA replication and the mechanism of initiation of viral[unreadable] RNA synthesis. Moreover, we will alter the surface structure of[unreadable] the poliovirion to achieve hybrid virus expressing foreign[unreadable] antigenic determinants in addition to those of poliovirus Type 1[unreadable] (Mahoney). Our studies may lead to the development of new[unreadable] vaccines and of novel drugs directed against picornavirus[unreadable] infection.[unreadable]